Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have successfully induced a hibernation-like state in tadpoles of the Xenopus laevis frog using donepezil (DNP), a drug already approved by the FDA for treating Alzheimer’s disease. This breakthrough, published in *ACS Nano*, represents a significant step forward in the potential use of DNP to protect organs during emergency medical situations.
Previously, the Wyss Institute team had achieved similar results using SNC80, a drug that extends the survival of whole mammalian hearts for transplants. However, SNC80 is not approved for human use due to its risk of causing seizures. In contrast, DNP, which has been in clinical use since 1996, offers a promising alternative that could be rapidly repurposed for medical emergencies to prevent irreversible organ damage while patients are transported to hospitals.
“Cooling a patient’s body to slow metabolic processes has been a long-standing practice in medical settings to reduce injury from severe conditions, but this can only be done in well-resourced hospitals,” said Michael Super, Ph.D., co-author of the study and Director of Immuno-Materials at the Wyss Institute. “Achieving a similar state of ‘biostasis’ with an easily administered drug like DNP could potentially save millions of lives every year.”
The research is part of the DARPA Biostasis Program, which aims to extend the critical “Golden Hour” following traumatic injury or acute infection. The Wyss Institute has been a key participant in this program since 2018, achieving significant milestones, including the identification of DNP as a potential candidate for inducing a torpor-like state.
Using predictive machine learning algorithms and animal models, the team identified DNP as a top candidate after the initial success with SNC80. Interestingly, clinical overdoses of DNP in Alzheimer’s patients have been associated with torpor-like symptoms, such as drowsiness and reduced heart rate, though this study is the first to explore these effects as a primary clinical response.
When tested on X. laevis tadpoles, DNP successfully induced a reversible torpor-like state but showed some toxicity, accumulating in the animals’ tissues. To address this, the researchers encapsulated DNP in lipid nanocarriers, which reduced toxicity and targeted the drug to brain tissue, a promising outcome given the brain’s role in mediating hibernation.
While these findings are promising, the researchers caution that further studies are needed to fully understand DNP’s mechanisms and to scale up production for potential use in larger animals and humans. Senior author Donald Ingber highlighted that DNP‘s established clinical use and manufacturing methods, combined with the safety of lipid nanocarriers, suggest that an encapsulated version of the drug could be rapidly developed for emergency medical applications.
